CA2020986A1 - Halogenated pyrimidine 3-oxide derivatives, their use for the treatment and prevention of hair loss and for stimulating its regrowth - Google Patents

Abstract

Compounds of formula: <IMAGE> in which: R1 and R2 denote, independently of each other, a hydrogen atom or a carbamoyl group of formula: <IMAGE> with R'3 denoting hydrogen or R3; an alkoxycarbonyl group of formula: <IMAGE> or an acyl group of formula: <IMAGE> in which R3 denotes an alkyl, alkenyl or cycloalkyl radical; R3 may also denote an aryl or aralkyl radical; R denotes a linear or branched C1-C6 alkyl radical substituted by one or more halogen atoms, and their use for the treatment and prevention of loss of hair and for stimulating its regrowth.

Description

2 17 ~

The present invention relates to new halogenated pyrimidine oxide-3 derivatives, to the preparation cosmetic or pharmaceutical compositions intended in particular to be used in topical application in the treatment and prevention of hair loss and to stimulate their regrowth.
We already know in the state of the art the piperidino-6 diamino-2,4 pyrimidine oxide-3 or "Minoxidil"
for its use in the treatment of fall of hair, alopecia areata, scaling dermatitis, alopecia, etc.
The Applicant has just discovered new products derived from pyrimidine oxide-3, substituted in position 6 by a haloalkoxy group.
She discovered that these products were parti-particularly effective for the treatment of regrowth hair and in particular to induce and stimulate hair growth and curb their fall and they could in particular be used in the treatment of scalp diseases, such as alopecia areata, derma-flaking tit or alopecia.
Another advantage of these compounds is their solu-remarkable bility in environments used for the application topical cation.
The invention therefore relates to new derivatives of pyrimidine oxide 3 substituted in position 6 by a haloalkoxy group, as well as their preparation process tion.
The invention also relates to compositions cosmetics and / or pharmaceuticals enabling the work of these compounds.

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The compounds according to the invention are essential.
so characterized by the fact that they meet the formula:

R2HN \ ~ ~ NHRl (I) NOT

GOLD
in which:
R denotes an alkyl radical, linear or branched in Cl-C6, substituted by at least one halogen atom;
Rl and R2 independently denote one of the other, a hydrogen atom, a carbamoyl group of formula:
~ R3 - C - N. (B) OR ~ 3 with R '3 denoting a hydrogen atom or R3;
an alkoxycarbonyl group of formula:
- I - OR3 (C) or an acyl group of formula:
~ 11 ~ P`3 (D) in which R3 denotes a linear alkyl radical or amified in Cl-C18, a C -C alkenyl group a C5-C8 cycloalkyl group; R3 can also generate an aryl or aralkyl radical corresponding to the formula:

2 ~

~ - ~ 2 `(E) in which:
R4 and / or R5 ~ independently of one another, denote a hydrogen atom, an lower alkyl group laughing in Cl-C6, a hydroxyl group, alkoxy in Cl-C6, or a halogen atom, at least one of the radicals R4 or R5 being different from hydrogen;
n is an integer between 0 and 4;
as well as their cosmetic acid addition salts only or pharmaceutically acceptable.
Particularly preferred compounds are those in which the halogen atoms denote fluorine or chlorine; the C1-C6 alkyl group represented by R, designates in particular a mono- or polyhalomethyl group, -ethyl or -propyl; Rl and R2 preferably designating hydrogen.
The more particularly preferred R groups are chosen from the groupings -CH2CF3, -CH2-CF2-CHF2.
The more particularly preferred compounds of the invention are constituted by diamino-2,4 (trifluoro-2 ethyloxy) -6 pyrimidine oxide-3 and diamino-2,4 (tetrafluoro-2,2,3,3 propyloxy) -6 pyrimidine oxide-3.
The compounds according to the invention can also exist in the tautomeric form, meeting the formulas (IA) and (IB) below:

~ 3 OH OH
`` \ `~ R211N ~ NRl OR OR
(IA) (IB) These tautomeric forms of formulas (IA) and (IB) may be present in varying proportions and one may be preponderant over the others.
The compounds according to the invention for which Rl and R2 denote a hydrogen atom are prepa-res starting from diamino 2,4 (2,4-dichloro phenoxy) -6 pyrimidine oxide-3 or 2,4-diamino chloro-6 pyrimidine 3-oxide which is reacted with an alcoholate of formula RO ~ Y ~ where R has the meaning given above and Y is an alkaline cation such as sodium, potassium, lithium.
The compounds for which R1 and R2 are carbamoyl, alkoxycarbonyl or acyl groups are obtained from 2,4-haloalkoxy-6 diamino derivatives pyrimidine oxide-3 corresponding to which the preparation is described below.
Obtaining derivatives for which Rl and R2 are carbamoyl groups, is generally carried out by reacting a carbamoyl chloride on the drift diamino-2,4 haloalkoxy-6 pyrimidine oxide-3 corresponding in a polar solvent, such as dimethyl sulfoxide, to a temperature between 0 and 100C and more between 20 and 70C.

- 2 ~

Obtaining derivatives for which Rl and R2 are alkoxycarbonyl groups, is generally produced by the action of an excess of chloroformic ester on the 2,4-diamino derivative 6-haloalkoxy-3-pyrimidine oxide corresponding by operating in a polar aprotic solvent that, such as dichloromethane in the presence of an amine tertiary, such as triethylamine or pyridine, to a temperature between 0 and 50C.
Obtaining derivatives for which Rl and R2 are acyl groups, is generally carried out in reacting an acid chloride or an anhydride on the 2,4-diamino derivative 6-haloalkoxy pyrimidine oxide-3 corres-laying in an aprotic polar solvent such as dichloromethane, in the presence of a tertiary amine such than triethylamine or pyridine, at a temperature between 0 and 50C.
From the compounds of formula (I), it is possible prepare their acid addition salts cosmetically or pharmaceutically acceptable, such as the salts of sulfuric, hydrochloric, hydrobromic, phosphori-that, acetic, benzoic, salicylic, glycolic, succi-nique, nicotinic, tartaric, maleic, pamoic, methane sulfonic, picric, lactic, etc.
. The compounds according to the invention can be used in the cosmetic or pharmaceutical field, especially in topical applications, and more particularly in the treatment or prevention of the fall hair and more particularly alopecia areata, alopecia, as well as flaking dermatitis.

These compositions are essentially character because they contain in a medium physiologically acceptable, suitable for an application topical tion, at least one compound corresponding to the formula (I) or one of its salts.
These compositions may include as physiologically acceptable medium, any suitable medium for topical application, either in cosmetics or pharmacy, and that is compatible with the substance l.0 active.
The compounds according to the invention can be find in this medium, either in the dissolved state, or at the dispersed state, in particular in micronized form.
The compositions intended to be used in pharmacy come in the form of ointment, dye ture, cream, ointment, powder, patch, tam-soaked pon, solution, emulsion or vesicu-milk, lotion, gel, spray or suspension.
They can be either anhydrous or aqueous, depending on the clinical indication.
The compounds of formula (I) are present in these pharmaceutical compositions at concentrations preferably between 0.1 and 20% by weight, and particular between 0.2 and 10% by weight, compared the total weight of the composition.
The cosmetic compositions are especially intended to be used in the form of lotion, gel, soap, shampoo, aerosol or foam and contains . ,.
in a physiologically acceptable medium, at least one compound of formula (I) or one of its salts.

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The concentration of the compounds of formula (I) in these compositions is preferably between 0.01 and 15% by weight and in particular between 0.05 and 10% by weight, relative to the total weight of the composition.
The compositions according to the invention can contain various additives usually used in cosmetic or pharmacy and in particular substances these active ingredients, such as moisturizers like thiamorpholine and its derivatives or urea; anti agents seborrheics such as S-carboxymethylcysteine, S-benzylcysteamine and their derivatives; thioxolone.
The compounds according to the invention can be associated with compounds further improving their activity on regrowth and / or on braking the fall of hair, such as more particularly the compounds following:
- nicotinic acid esters, of which more particularly C1-C6 alkyl nicotinates and in particular methyl nicotinate;
- steroid anti-inflammatory agents and non-steroid well known in the art and in particular hydrocortisone, its salts and its derivatives, niflumic acid, etc .;
- retinoids and more particularly acid t-trans retinoic also called tretinoin, isotreti-nolne, retinol or vitamin A and its derivatives, such as acetate, palmitate or propionate, motretinide, etretinate, zinc t-trans retinoate;
- the antibacterial agents are chosen more particularly among the macrolides, pyranosides and tetracyclines and in particular erythromycin;

- calcium antagonistic agents, such as more particularly cinnarizine and diltiazem;
- hormones, such as estriol or analogues or thyroxine and its salts;
- antiandrogenic agents, such as oxendo-lone, spironolactone, diethylstilbestrol;
- OH radical sensors, such as dimethyl sulfoxide.
We can also associate with the compounds of the invention, possibly mixed with the others, compounds such as the diazoxide corresponding to methyl-3 chloro-7 2H benzothiadiazine 1,2,4-dioxide-1,1;
spiroxasone or 7- (acetylthio) -4 ', 5'-dihydrospiro [androst 4-ene-17.2 '- (3'H) furan] -3 one; phospholipi-, such as lecithin; linoleic and lininic acids lenique; salicylic acid and its derivatives described in French patent No. 2,581,542, and more particularly salicylic acid derivatives bearing a group alkanoyl having 2 to 12 carbon atoms in position 5 of benzene cycle; hydroxycarboxylic acids or ketocarboxylates and their esters, lactones and their corresponding salts; anthralin or trihydroxy-1,8,9 anthracene, carotenoids, eicosatetraynolic acids, their esters and amides.
The compounds according to the invention can also be associated with surfactants including more particularly those chosen from the agents nonionic and amphoteric surfactants.
Among the nonionic surfactants, mention will be made in particular the polyhydroxypropyl ethers described in the French patents Nos. 1. ~ 77,048; 2,091,516; 2,169,787;

~ 3 2,328,763; 2,574,786; oxyethyl- (C8-Cg) alkyl phenols born with 1 to 100 moles of ethylene oxide and preferably 5 to 35 moles of ethylene oxide; alkylpoly-glycosides of formula:

CnH2n. ~ L (c6Hl0o5) X
in which n varies from 8 to 15 inclusive and x from 1 to 10 included.
Among the amphoteric surfactants, will more particularly cite the amphocarboxyglycinates and amphocarboxypropionates defined in the dictionary CTFA, 3rd edition, 1982, and sold, in particular, under the MIRANOL trademark by the MIRANOL Company.
The compounds according to the invention can be introduced in supports which further improve the activity vite at the level of regrowth, presenting at the same time cosmetically advantageous properties, such as ternary volatile mixtures of alkylene alkyl ether-glycol or dialkylene glycol (alkyl and alkylene of preferably in Cl to C4), ethyl alcohol and water, the glycolic solvent designating more particularly the monoethyl ether of ethylene glycol, monomethyl ether of propylene glycol, the monoethyl ether of diethylene glycol.
The compounds according to the invention can also be introduced. in gelled supports or thickened, such as essentially aqueous supports gelled by heterobiopolysaccharides, such as xanthan gum or cellulose derivatives, sup-hydroalcoholic ports gelled with polyhydroxy ethyl-acrylate or methacrylate or essentially aqueous supports thickened, in particular by polyacrylic acids.

ques crosslinked by a polyfunctional agent, such as those sold under the trademark CARBOPOL by the Company GOODRICH.
These compositions can also contain preservatives, stabilizers, agents pH regulators, pressure modifiers osmotic, emulsifying agents, UVA filters and UVB, antioxidant agents such as ~ -tocopherol, butylhydroxyanisole, butylhydroxytoluene.
The physiologically acceptable medium can be consisting of water or a mixture of water and a solvent or a mixture of solvents, the solvents being chosen among the internationally acceptable organic solvents cosmetic or pharmaceutical and chosen more particular-ment among the lower alcohols in Cl-C4, such as alcohol ethyl, isopropyl alcohol, tert-butyl alcohol that al ~ ylèneglycols, alkylethers of alkylene glycol and dialkylene glycol, such as monoethyl ether ethylene glycol, propylene glycol monomethyl ether, diethylene glycol monoethyl ether. Solvents, when present, are present in proportions between 1 and 80% by weight relative to the weight total of the composition.
Physiologically acceptable media can be thickened using usual thickening agents-used in cosmetics or pharmacy, and we can more particularly mention heterobiopolysaccharides such than xanthan gum, scleroglucans, derivatives cellulose such as cellulose ethers, polymers acrylic, crosslinked or not.

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Thickeners are preferably present in proportions of between 0.1 and 5% by weight, and in particular between 0.4 and 3% by weight, relative to the total weight of the composition.
The invention also relates to a method of cosmetic treatment of hair or scalp, consisting in applying to them at least one composition such as defined above, in order to improve the aesthetics of the hair.
Another object of the invention is constituted by the use of the composition defined above, for the preparation of a drug which has the effect of inducing or stimulate hair growth and curb hair growth fall.
Treatment mainly involves applying on the alopecic areas of an individual's scalp, the composition as defined above.
The preferred mode of application is to apply quer 1 to 2 g of the composition on the alopecic zone, a frequency of one to two applications per day, during 1 to 7 days a week and this for a period of 1 to 6 mols.
The compositions can in particular be used in the treatment of alopecia areata, hair loss, flaking dermatitis.
The following examples are intended to illustrate the invention without, however, having a limited character.
tative.

Diamino-2,4 (tetrafluoro-2,2,3,3 propyloxy) -6 pyrimidine oxide-3 2 g of sodium are introduced into 100 g of tetraEluoro-2,2,3,3 propanol at 40 C. After addition of 10 g of 2,4-diamino-6 chloro-pyrimidine oxide-3, the mixture reaction is maintained 32 hours at 90C.
The reaction medium is cooled to 0 C and then filtered to remove an insoluble material. The residue of evapora-When the filtrate is dry, it is taken up in 100 cm3 of hexane. An insoluble material is removed by filtration. The expected product is obtained after dry evaporation of the filtrate. After recrystallization, 11 g of a white powder are obtained, melting at 148C.
Elementary analysis for C7H ~ F4N4O2 CHNF
Calculated 32.82 3.15 21.87 29.67 Found 32.65 3.24 21.80 29.60 H NMR spectrum conforms to structure expected.

Diamino-2,4 (2-trifluoroethyloxy) -6 pyrimidine oxide-3.

3 y of sodium are introduced into 50 ml of trifluoroethanol at 40 C. After addition of 10 g of diamino-2,4 chloro-6 pyrimidine oxide-3, the reaction mixture tional is maintained 20 hours at 85C.
The reaction medium is cooled to 0 C and then filtered to remove an insoluble material. The residue of evapora-dry filtration of the filtrate is taken up in dichloromethane and then in hexane in order to remove the trifluoroethanol having not reacted. The expected product in the form of white dre is hot recrystallized from acetonitrile.
4.2 g are obtained. It melts at 205 C.
Elementary analysis for C6H7F3N4O2 CHNF
Calculated 32.15 3.15 25.00 25.43 Found 31.67 2.97 24.67 25.08 The H NMR spectrum conforms to the structure expected.

The following composition is prepared:
- Diamino-2,4 (tétrafluoro-2,2`, 3,3 propyloxy) -6 pyrimidine oxide-3 6.0 g - Absolute ethanol / propylene mixture glycol (95/5) qsp100,0 g The following composition is prepared:
- 2,4-Diamino (2-trifluoroethyloxy) -6 pyrimidine oxide-3 10.0 g 20 - Propyleneglycol 20.0 g - Ethanol 50.0 g - Water qs100.0 g These two compositions are in the form of lotion.
1 to 2 g of this composition are applied to alopecic areas of the scalp, possibly accompanied by a massage to promote penetration, one to two applications per day for 3 months treatment.

``: s ~ 3 ~

In the same way, compositions are prepared under form of lotion in accordance with Example 2, replacing the pyrimldine oxide-3 derivative by the compounds respectively se of examples of preparation 3 and 4 ~

E ~ PREPARATION SAMPLE 3 , Diacetamido-2,4 (trifluoro-2 ', 2', 2'ethoxy) -6 pyrimidine N-oxide-3.
In a 250 ml three-necked flask saturated in atmosphere of argon, 90 ml of dichloromethane, 11.1 g of triethylamine and 6 g of 2,4-diamino (trifluoro-2 ', 2', 2 ' ethoxy) -6 pyrimidine N-oxide 3. Add dropwise to drop in the mixture cooled between 0 and 5C, 8.65 g of chlo-acetylure.
After 8 hours 30 minutes of reaction, the reaction medium by:
- 2 x 40 ml of water - 60 ml of a 1% Na2CO3 solution - 2 x 40 ml of water.
The organic phase is dried over Na2SO4. ~ close Na2SO4 flltration, the flltrate is concentrated at the tlers of solvent. The product is preflected by adding 250 ml of hexane. The latter is recrystallized from a mixture hexane-acetone 1/2.
2.25 g of diacetamido-2,4 (trifluoro-2 ', 2', 2'ethoxy) -6 pyrimidine N-oxide-3.
Yield = 27%
PF = 183-185C.

7. ~

Elementary analysis for CloHllF3N4O4; M = 308 ~ 2 g.
CHNF
Calculated 38.97 3.6018.18 18.49 Found 39.55 3.6618.11 18.05 CH ~
~ H

Y - N ~ F
~ \ F
~ F
~ 0 The H NMR mass spectra are in accordance with the expected structure.

Dimethoxycarbonylamino-2,4 (trifluoro-2 ', 2', 2'ethoxy) -6 pyrimidine N-oxide-3.
In a 250 ml three-necked flask saturated in atmosphere of aryon, 60 ml of dichloromethane, 16.7 g of triethylamine and 6 g of 2,4-diamino (trifluoro-2 ', 2', 2 ' ethoxy) -6 pyrimidine N-oxide-3. We add to this mixture ge 15.6 g of methyl chloroformate drop by drop between 0 and 5C.
After 16 hours of stirring at room temperature te, the reaction medium is washed with:

- 4 x 20 ml of a 1% HCl solution - 3 x 20 ml of water (until the phase is neutral aqueous).

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The organic phase is dried over Na2SO4 and the solvent is evaporated in vacuo. The crude collected is taken up in 50 ml of ethyl ether and filtered. After evaporation of the filtrate, a viscous liquid is obtained which is brought to reflux in 80 ml of methanol. It is formed a precipitate which is filtered hot and dried under vacuum and on P2O5 for 12 hours.
5.4 g of dimethoxycarbonyl are thus collected amino-2,4 (trifluoro-2 ', 2', 2'ethoxy) -6 pyrimidine N-oxide-3.
Efficiency = 59%
PF = 184,185 C.
Elementary analysis for CloHllF3N4o6 i M 340 ~ 2 g-CHNF

Calculated 35.30 3.2616.47 16.75 Found 35.36 3.2116.27 16.78 O, ~ - 3 ~ O
~ H
- + ~

~ F

>, Q \
o CH3 ~ H NMR mass spectra are in accordance with the expected structure.

Claims (31)

1. The compounds corresponding to the general formula:

(I) in which:
R denotes an alkyl radical, linear or branched in C1-C6, substituted by at least one halogen atom;
R1 and R2 independently denote one of the other, a hydrogen atom or a group carbamoyl of formula:

with R'3 denoting a hydrogen atom or R3;
an alkoxycarbonyl group of formula:

or an acyl group of formula:

in which R3 denotes a linear alkyl radical or branched at C1-C18, a C2-C18 alkenyl group, a C5-C8 cycloalkyl group; R3 can also generate an aryl or aralkyl radical corresponding to the formula:

in which:
R4 and / or R5, independently of each other, denote a hydrogen atom, an lower alkyl group C1-C6 laughing, a hydroxyl group, C1-C6 alkoxy, or a halogen atom, at least one of the radicals R4 or R5 being different from hydrogen;
n is an integer between 0 and 4;
as well as their cosmetic or acid addition salts pharmaceutically acceptable. 2. Compounds according to claim 1, characterized by the fact that R denotes a mono- or polyhalo- group methyl, -ethyl or propyl, and the halogen atoms denote fluorine or chlorine atoms. 3. Compounds according to claim 1, characterized by the fact that R denotes a group -CH2CF3 or -CH2-CF2-CHF2. 4. 2,4-Diamino (2-trifluoroethyloxy) -6 pyrimidine oxide-3. 5. Diamino-2,4 (tétrafluoro-2,2,3,3 propyloxy) -6 pyrimidine oxide-3. 6. Composition intended for use in applications topical tion, characterized by the fact that it contains, in a physiologically acceptable environment, at least one compound of formula (I) as defined in the claim tion 1 or one of cosmetically acid addition salts or pharmaceutically acceptable. 7. Composition intended to be used in applica-topical tion, characterized by the fact that it contains minus a compound of formula (I) in which R denotes a mono- or polyhalomethyl, -ethyl or propyl group, and halogen atoms denote fluorine atoms or chlorine. 8. Composition intended to be used in applica-topical tion, characterized in that it contains a minus a compound of formula (I) in which R denotes -CH2CF3 or -CH2-CH2-CHF3 groups. 9. Composition intended to be used in applica-topical tion, characterized by the fact that it contains title of compound of formula (I) 2,4-diamino (2-trifluoro ethyloxy) -6 pyrimidine oxide-3. 10. Composition intended to be used in applica-topical tion, characterized by the fact that it contains title of compound of formula (I) diamino-2,4 (tetrafluoro-2,2,3,3 propyloxy) -6 pyrimidine oxide-3. 11. Composition according to claim 6, 7, 8, 9 or 10, intended for use in pharmacy, characterized by the fact that the compound of formula (I) is present in a proportion of between 0.1 and 20% by weight, per relative to the total weight of the composition. 12. Composition according to claim 6, 7, 8, 9 or 10, intended for use in pharmacy, characterized by the fact that the compound of formula (I) is present in a proportion of between 0.2 and 10% by weight, per relative to the total weight of the composition. 13. Composition according to claim 6, 7, 8, 9 or 10, intended for use in pharmacy, characterized by the fact that it is in the form of an ointment, tincture, cream, ointment, powder, patch, soaked tampon, solution, emulsion, vesicu-milk, lotion, gel, spray or suspension anhydrous or aqueous, for its pharmaceu-tick. 14. Composition according to claim 6, 7, 8, 9 or 10, intended for use in pharmacy, characterized by the fact that it is in the form of an ointment, tincture, cream, ointment, powder, patch, soaked tampon, solution, emulsion, vesicu-milk, lotion, gel, spray or suspension anhydrous or aqueous, with a view to its pharmaceutical application that, and that the compound of formula (I) is present in a proportion between 0.1 and 20% by weight relative to the total weight of the composition. 15. Composition according to claim 6, 7, 8, 9 or 10, intended for use in pharmacy, characterized by the fact that it is in the form of an ointment, tincture, cream, ointment, powder, patch, soaked tampon, solution, emulsion, vesicu-milk, lotion, gel, spray or suspension anhydrous or aqueous, with a view to its pharmaceutical application that, and that the compound of formula (I) is present in a proportion between 0.2 and 10% by weight relative to the total weight of the composition. 16. Composition according to claim 6, 7, 8, 9 or 10, intended for use in cosmetics, characterized by the fact that the compound of formula (I) is present in a proportion of between 0.01 and 15% by weight per relative to the total weight of the composition. 17. Composition according to claim 6, 7, 8, 3 or 10, intended for use in cosmetics, characterized by the fact that the compound of formula (I) is present in a proportion of between 0.05 and 10% by weight per relative to the total weight of the composition. 18. Composition according to claim 6, 7, 8, 9 or 10, intended for use in cosmetics, characterized by the fact that it comes in the form of a lotion, gel, soap, shampoo, aerosol or foam. 19. Composition according to claim 6, 7, 8, 9 or 10, intended for use in cosmetics, characterized by the fact that it comes in the form of a lotion, gel, soap, shampoo, aerosol or foam, and that the compound of formula (I) is present in a proportion between 0.01 and 15% by weight, relative to the total weight of the composition. 20. Composition according to claim 6, 7, 8, 9 or 10, intended for use in cosmetics, characterized by the fact that it comes in the form of a lotion, gel, soap, shampoo, aerosol or foam, and that the compound of formula (I) is present in a proportion between 0.05 and 10% by weight, relative to the total weight of the composition. 21. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it also contains minus a hydrating or antiseborrheic agent. 22. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it also contains minus an additional activity enhancing agent at level of regrowth and / or braking of the fall of hair. 23. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it also contains minus an additional activity enhancing agent at level of regrowth and / or braking of the fall of hair, said additional agent being chosen from the group consisting of nicotinic acid esters, steroidal or nonsteroidal anti-inflammatory agents, retinoids, antibacterial agents, agents calcium antagonists, hormones, anti-agents androgens and OH radical scavengers. 24. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it also contains minus an additional activity enhancing agent at level of regrowth and / or braking of the fall of hair, said additional agent being chosen from the group consisting of diazoxide, spiroxasone, phospholipids, linolenic and linoleic acids, salicylic acid and its derivatives, hydroxy acids carboxylic or ketocarboxylic, their esters, lactones and their corresponding salts, anthralin or trihydroxy-1,8,9 anthracene, carotenoids, acids eicosatetraynoic-5,8,11,14 eicosatriynoic-5,8,11, their esters and amides. 25. The composition of claim 6, 7, 8, 9 or 10, characterized in that the physiological environment mentally acceptable consists of water, a mixture water and at least one pharmaceutical organic solvent-ment or cosmetically acceptable or by a mixture of organic solvents pharmaceutically or cosmetically acceptable. 26. Composition according to claim 6, 7, 8, 9 or 10, characterized in that the physiological environment mentally acceptable consists of water, a mixture water and at least one pharmaceutical organic solvent-ment or cosmetically acceptable or by a mixture of organic solvents pharmaceutically or cosmetically acceptable, the organic solvent being chosen from the group made up of lower C1-C4 alcohols, alkylene glycols, alkyl ethers of mono- and dialkylene glycol. 27. Composition according to claim 6, 7, 8, 9 or 10, characterized in that the physiological environment thickened with thickening agents healthy and / or gelling agents and also contains at least one physiologically acceptable adjuvant selected from the group made up of conservative agents, agents stabilizers, pH regulating agents, agents osmotic pressure modifiers, emulsifiers fiants, UVA and UVB filters, and anti-oxidants. 28. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it also contains minus one surfactant selected from the group consisting of killed by nonionic surfactants and ampho-mothers. 29. Composition according to claim 6, 7, 8, 9 or 10, characterized in that it is intended to be used as a medicine in the treatment of canique of hair loss. 30. Use of a composition as defined in claim 6, 7, 8, 9 or 10, for the preparation tion of a drug intended for use in the treatment therapeutic treatment of hair loss. 31. Method for cosmetic treatment of hair or scalp, characterized by the fact that one applies a composition as defined in claim 6, 7, 8, 9 or 10.